The overall goal of this collaborative research project between researchers at Johns Hopkins University and Beijing Hospital is to validate a novel comprehensive MRI exam protocol, including pH, diffusion, and perfusion imaging, for the assessment of ischemic stroke and recovery from stroke. Stroke is a leading cause of death and disability among adults worldwide, second in China and fourth in the US. Currently, the only FDA- approved treatment for ischemic stroke is intravenous tissue plasminogen activator (IV tPA) that is given within three hours of symptom onset. Patients who present beyond three hours after stroke onset are now treated in several clinical trials only. However, the selection criteria for this type of therapy are still not well defined. This is further complicated by the unfortunate fact that patients who receive tPA are at increased risk for hemorrhage. Thus, the benefit versus risk with tPA should be assessed on an individual basis, based on the presence and extent of an ischemic penumbra, defined as tissue that is still viable but at risk of infarctio. APT imaging is an entirely new MRI methodology that can non-invasively detect tissue pH. This totally noninvasive pH imaging method can identify regions of tissue acidosis following impaired aerobic metabolism. We hypothesize that the pH-weighted imaging (pHWI) deficit in stroke, due to tissue acidosis, predicts the maximum final infarction size if no reperfusion is initiated, and he addition of APT-pH imaging to the perfusion/diffusion MRI protocol could better visualize an ischemic penumbra, thus improving predictions about final infarct size and outcome. We will test our hypothesis on animals, using a clinically relevant middle cerebral artery occlusion model, and perform pilot human scanning on hyperacute and acute ischemic stroke patients to assess the possible utility of this new technique in the clinic. Our specific aims are: (i) to assess the characteristics and spatio-temporal evolution of perfusion/pH/diffusion deficits in rat brain ischemia/reperfusion models; and (ii) to determine the radiologic characteristics and clinical values of pH imaging of hyperacute and acute ischemic stroke patients. If the hypotheses are proven correct, we expect to have an additional marker that can be used for diagnosis and prognosis of stroke patients in the clinic.